The ATTENUATION study targets patients with gastric adenocarcinoma (GA), esophageal adenocarcinoma (EAC) or gastro-esophageal junction (GEJ) who have received 4 cycles of FLOT chemotherapy before the surgery. Standard post-operative management consists of chemotherapy with 4 cycles of FLOT.
However, the nature and duration of postoperative treatment are standardized and are not adapted to the specific tumor response of each patient. All patients are therefore referred to the same treatment regimen.
As a result, good responders (defined in particular by wide resection of the tumor and a good response to preoperative chemotherapy on the tumor removed during surgery) may be over-treated and exposed to unnecessary adverse events.
Only 50-60% of patients can start chemotherapy post-operatively, due to the potential residual adverse effects associated with surgery in particular. Thus, it would appear that preoperative chemotherapy is the most important factor in the overall efficacy of the treatment sequence. Moreover, numerous retrospective studies have reported a favorable outcome in patients with a major response to pre-operative treatment but who were unable to receive post-operative chemotherapy.
The hypothesis of this study is that surveillance after surgery in patients with gastric or gastroesophageal junction tumors, with a good response to preoperative chemotherapy could provide significant clinical benefit and favorable disease progression.
Participants will:
* be distributed in one of the two arms * will be followed up every 3 months for 2 years, then every 6 months (clinical examination, imaging, quality-of-life questionnaire) subsequent years until 3 years after the randomization of the last patient. * followed up until their death or their progression whether local, regional or metastatic.
I1. Age ≥ 18 years, I2. Histologically proven non-metastatic (M0) gastric, oesophageal or gastroesophageal junction adenocarcinoma, I3. Subjects must have completed both pre-operative chemotherapy with a fluoropyrimidine-platinum containing regimen (FLOT 4 cycles) and microscopically complete (R0) resection prior to randomization.
Absence of lymph node involvement (ypN0), assessed on a min. of 16 or 7 lymph nodes according to the localization and,
Either ypT0-2 (all TRG grade) or ypT3 (with TRG 1a-b according to Becker classification or TRG1-2 according to Mandard's classification), I5. ECOG Performance Status 0-1, I6. Patients fit to receive post-operative chemotherapy, I7. Interval between the date of surgery and the date of randomization no longer than 10 weeks, I8. Adequate organs function defined as : Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L; Haemoglobin ≥ 9 g/dL (without transfusion within 7 days); Serum creatinine AND Calculated creatinine clearance as per MDRD or CKD-EPI formula ≤ 1.5 upper limit of normal (ULN) AND ≥ 40 mL/min /1.73m²; Serum total bilirubin ≤ 1.5 ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤ 3ULN is acceptable); AST and ALT ≤ 3 ULN; International Normalized Ratio (INR) and activated Partial Thromboplastin Time (aPTT)≤ 1.5 ULN .
E1. Oesophageal squamous cell carcinomas, E2. Tumour with Deficient MisMatch Repair (MMR) and/or Microsatellite Instability status, E3. Dihydro Pyrimidine Dehydrogenase (DPD) deficiency, NB: if not previously done, the following blood chemistry level must be perform at screening, : blood uracil level - uracilemia dosing result is mandatory prior the inclusion E4. Persistent toxicities related to prior treatment of grade>1, E5. QTcF longer than 450 msec for men and longer than 470 msec for women, E6. Hypokalemia OR Hypomagnesemia OR Hypocalcemia Grade>1
Known history of hypersensitivity to fluorouracil, oxaliplatin, docetaxel or calcium folinate to any of their excipients, according to the SmPCs of these products OR
Peripheral sensory neuropathy with functional impairment prior to first treatment according the SmPC of oxaliplatin OR
Clinically significant active heart disease or myocardial infarction within 6 months OR
Parallel
observation alone
Other interventionPatient will not received post-operative chemotherapy. There will be only surveillance until progression.
3 year Overall Survival rate
The primary endpoint will the 3-year Overall Survival (OS) rate, described as the proportion of patients still alive 3 years after the date of randomization.
3 year disease-free survival rate
The co-primary endpoint is the 3-year Disease-Free Survival rate, considered as a binary variable with a success defined as being relapse-free at 3 years.
Overall survival
The overall survival (OS) will be defined as the time from the date of randomization to the date of death due to any cause or to the date of last contact if patient is still alive (censored patients).
Disease-Free Survival (DFS)
The Disease-Free Survival (DFS) will be defined as the time from the date of randomization to the date of the first documented relapse of the disease or death due to any cause, whichever occurs first. Patients alive and disease-free at the time of the analysis will be censored at the date of their last tumoral evaluation.
Type of Relapses
The relapses will be described by their location (either locoregional or distant relapse).
The tolerability profile
The tolerability profile will be assessed continuously using the NCI-CTC AE version 5.0. All Adverse Events (AE), whichever their relationship with study treatments, all Serious AE, all Suspected Unexpected Serious Adverse Reactions and all toxic deaths, will be reported.
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